TY - JOUR
T1 - Challenges for drug studies in children
T2 - CYP3A phenotyping as example
AU - de Wildt, Saskia N.
AU - Ito, Shinya
AU - Koren, Gideon
N1 - Funding Information:
Dr de Wildt's research is supported by a Ter Meulen Fund stipend from Royal Netherlands Academy of Research and a Restracomp Grant from the Hospital for Sick Children's Research Institute. Dr Koren is holder of the Research Leadership for Better Pharmacotherapy during pregnancy and lactation at the University of Toronto and the Ivey Chair in Molecular Toxicology, the University of Western Ontario. This research is partially supported by grants from CIHR (Drs Koren and Ito).
PY - 2009/1
Y1 - 2009/1
N2 - A paucity of data exists on the disposition and effect of drugs in young children. This information gap can be reduced by elucidating developmental principles of absorption, distribution, metabolism and excretion (ADME) in vivo. Such knowledge might enable the prediction of the disposition of individual drugs in children over the whole pediatric age range. CYP3A, the most abundant human drug metabolizing enzyme, is involved in the metabolism of more than 50% of all marketed drugs. Hence, elucidating the developmental pattern of CYP3A in relation to genetic background, disease and comedications might greatly enhance our knowledge on drug disposition in children. Several methods have been used to determine in vivo CYP3A activity in human adults, while similar studies in children face several ethical, practical and scientific challenges. The aim of this review is to identify these challenges and offer feasible solutions for studying drugs in young children, with an emphasis on CYP3A phenotyping as an example.
AB - A paucity of data exists on the disposition and effect of drugs in young children. This information gap can be reduced by elucidating developmental principles of absorption, distribution, metabolism and excretion (ADME) in vivo. Such knowledge might enable the prediction of the disposition of individual drugs in children over the whole pediatric age range. CYP3A, the most abundant human drug metabolizing enzyme, is involved in the metabolism of more than 50% of all marketed drugs. Hence, elucidating the developmental pattern of CYP3A in relation to genetic background, disease and comedications might greatly enhance our knowledge on drug disposition in children. Several methods have been used to determine in vivo CYP3A activity in human adults, while similar studies in children face several ethical, practical and scientific challenges. The aim of this review is to identify these challenges and offer feasible solutions for studying drugs in young children, with an emphasis on CYP3A phenotyping as an example.
UR - http://www.scopus.com/inward/record.url?scp=58149121289&partnerID=8YFLogxK
U2 - 10.1016/j.drudis.2008.07.007
DO - 10.1016/j.drudis.2008.07.007
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.systematicreview???
C2 - 18721895
AN - SCOPUS:58149121289
SN - 1359-6446
VL - 14
SP - 6
EP - 15
JO - Drug Discovery Today
JF - Drug Discovery Today
IS - 1-2
ER -